Chfr, also known as Checkpoint with Forkhead-associated and RING finger domains, is a cell cycle-related E3 ubiquitin ligase. It plays a role in controlling chromosomal instability and is involved in a checkpoint regulating entry into mitosis [1,4]. DNA methylation can silence its expression, and its abnormal regulation has implications for various biological processes and diseases.

In a study on endothelial cells, ChfrΔEC (endothelial cell-restricted Chfr knockout) mice showed augmented VE-cadherin expression and abrogation of LPS-induced VE-cadherin degradation, suggesting Chfr's role in regulating the endothelial junctional barrier in inflammation [2]. In triple-negative breast cancer, CHFR was identified as a negative regulator of ZEB1, with functional studies revealing that CHFR decreased ZEB1 expression in a ubiquitinating-dependent manner, leading to significant cell death under chemotherapy [3].

In conclusion, Chfr has diverse functions including its role in the cell cycle and ubiquitin-mediated protein degradation. The use of gene knockout mouse models, like the ChfrΔEC mice, has provided valuable insights into its role in specific biological processes such as endothelial function and in diseases like breast cancer. These studies help to understand the underlying mechanisms and may offer potential therapeutic targets.